Expandable body having deployable microstructures and related methods

ABSTRACT

Apparatuses, systems and methods for treating a patient by positioning an expandable body ( 10 ) having one or more microstructures ( 14 ) within a body lumen and penetrating the lumen wall with the microstructures ( 14 ). The microstructures are formed in or attached to the lumen through a cacheter or other suitable device. Each microstructure ( 14 ) has an end ( 16 ) which is attached to the expandable body and a free end ( 18 ). Once the apparatus is positioned within the body lumen in a desired location one or more of the microstructures are deployed wherein the free ends project radially outwardly. The free ends of the deployed microstructures penetrate the lumen wall by continued expansion of the body. Additionally, a therapeutic agent may be delivered to the lumen wall by the penetrated microstructures.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims the benefit and priority of U.S. ProvisionalPatent Application No. 60/395,180 (Attorney Docket 021258-000900US)filed Jul. 11, 2002, and U.S. Provisional Patent Application No.60/421,404 (Attorney Docket 021258-000910US) filed Oct. 24, 2002, thefull disclosures of which are hereby incorporated by reference for allpurposes.

Also, this application is related to PCT Patent Application No.______(Attorney Docket 021764-000720PC), filed on the same day as thisapplication, the full disclosure of which is hereby incorporated byreference for all purposes.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH AND DEVELOPMENT

NOT APPLICABLE

REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAMLISTING APPENDIX SUBMITTED ON A COMPACT DISK.

NOT APPLICABLE

BACKGROUND OF THE INVENTION

The present invention relates to apparatuses, systems and methods oftreating a patient. Particularly, the present invention relates totreating a body lumen. More particularly, the present invention relatesto treating a blood vessel, such as in the treatment of heart disease.

Heart disease continues to be a leading cause of death in the UnitedStates. The mechanism of this disease is often progressive narrowing ofcoronary arteries by atherosclerotic plaque which can lead to acutemyocardial infarction and disabling angina. Techniques to treat coronaryatherosclerosis include percutaneous transluminal coronary angioplasty,(or PTCA, commonly referred to as balloon angioplasty), atherectomy, andcoronary stenting. In each of these techniques, a guidewire is threadedto the site of coronary blockage and a treatment catheter is advancedover the guidewire. In balloon angioplasty, the guidewire is passedthrough the blockage and a balloon catheter is positioned within theblockage. The balloon is then inflated, compressing the atheroscleroticplaque against the walls of the coronary artery. In atherectomy, thetreatment catheter is equipped with a cutting device which cuts theplaque away as the catheter is advanced through the blockage. Instenting, a stent, such as a metal or wire cage-like structure, isexpanded and deployed against the plaque. Such stenting may be performedafter balloon angioplasty or simultaneously with balloon angioplastywherein the stent is mounted on the balloon. In each of thesetreatments, compression of the plaque and expansion of the coronaryartery, or removal of the atherosclerotic plaque, often restores lumenpatency.

Despite the overall initial success of these procedures, many patientsundergoing these therapeutic procedures to clear blocked coronaryarteries will suffer restenosis (re-blockage) at some point after theinitial procedure. Such restenosis may be a manifestation of the generalwound healing response. The injury induced by coronary intervention maycause platelet aggregation, inflammatory cell infiltration and releaseof growth factors, followed by smooth muscle cell proliferation andmatrix formation. Thus, intimal hyperplasia due to vascular injury maybe involved in the etiology of restenosis.

In an effort to inhibit such restenosis, numerous pharmacological agentsand genes have been delivered to such arteries. Although agents andgenes have been shown to inhibit restenosis in animal models, many havefailed in human trials. One explanation for their failure is thatsuboptimal doses of agents were used in order to prevent side effectswhich occur from systemic administration of the higher doses.Consequently, the concept of localized intravascular delivery oftherapeutics has become an attractive solution to overcome thislimitation.

However, therapeutic agents coating conventional stents may havedifficulty controllably passing into the vessel wall. As mentioned,stents mechanically prevent elastic recoil of the compressed plaque. Atypical conventional stent is shown in FIGS. 1-2. FIG. 1 shows thecoronary stent before expansion and FIG. 2 shows the stent afterdeployment. The stent consists of a metal lattice I with interstices 2.In use, a conventional balloon angioplasty procedure is often firstperformed to create a larger lumen in an occluded vessel, illustrated inFIG. 3A showing plaque 3 inside a coronary artery 4. Then, using asecond balloon, the stent can be expanded at the site of the occlusionto a diameter slightly larger than the normal inner diameter of thevessel. The metal lattice 1 holds the compressed plaque against thevessel wall, as shown in FIG. 3B. If therapeutic agents are presentcoating the stent 1, the agents can pass into the vessel wall 4 on theright side, where there is little or no plaque, but agent penetrationmay be inhibited by the plaque 3 built up on the left side of theartery. The thickness of residual plaque in patients with coronaryartery disease following angioplasty and stent placement may be in therange from 100 to 200 μm thick. In order to prevent restenosis, genes ordrugs placed on the surface of a stent may benefit from a mechanism topenetrate the layer of compressed plaque barrier to gain entry to thevessel wall, particularly through the internal elastic lamina into themedia and/or adventitia where the biology of restenosis resides.

In an effort to overcome the above described shortcomings, methods andapparatuses for drug and gene delivery are provided by Reed et al. (U.S.Pat. No. 6,197,013), incorporated by reference herein for all purposes.The Reed et al. devices allow diffuse delivery of a drug or gene to thecoronary artery. This is accomplished by arrays of micromechanicalprobes present on the surface of the devices which penetrate the plaqueand allow for efficient transport of therapeutic agents into the arterywall, in some cases directly to the artery media. The direct injectionof therapeutic agents through the atherosclerotic plaque into the arterywall enables a wider variety of pharmaceuticals to be used when comparedto the drugs used in current drug eluting stents. The probes can be partof a coronary stent which remains in the artery, or can be part of theangioplasty balloon, which is removed after the interventionalprocedure. The Reed et al devices differ from conventional methods inthat a direct physical penetration of vascular plaque is accomplished.

While the Reed et al. devices represents a significant advancement,still further improvements would be desirable. The drug deliveringprobes of the Reed et al. devices preferably extend between 25 micronsand 1000 microns from a surface of a deployment mechanism, such as avascular stent, angioplasty balloon or an electrophoretic device. Inmost embodiments, particularly those including vascular stents, theprobes extend this distance from the surface in the undeployed position.Deployment of the deployment mechanism involves radial force that pushesthe probes such that they penetrate the vessel wall. The deploymentmechanism preferably includes a removable housing, such as a sheath, inwhich the probes are disposed when the housing is in a closed state butis separate from the probes when the probes are deployed. This housingstructure and the enclosed probes increase the minimum size of thedeployment mechanism and possibly the risk of trauma to the vessel wall.Further, the designs of the Reed et al. devices suggest siliconmicromachining techniques to produce the probes rather than conventionallaser machining. It would be desirable to provide systems and deviceshaving a lower profile for introduction to the blood vessel or bodylumen. This would reduce the overall size of the device and possiblyreduce the risk of trauma upon introduction to the vessel. Further itwould be desirable to provide devices which may be produced byconventional laser machining.

In addition, it would be desirable to provide systems and devices whichwould secure the device in place and provide a mechanical seal to thevessel wall. One drawback of many conventional stents is the tendency ofsuch stents to migrate downstream from the initial placement area. Forexample, due to irregularity in the vessel diameter or underexpansion ofthe stent, such stents have been observed to migrate downstream from theinitial placement area. Thus, not only is the objective of the stentimplantation not achieved, but the migrating stent may cause injuryelsewhere in the vascular system. Further, a problem associated withgrafts used for endovascular repair, particularly of aneurysms, ispostprocedural leakage around the graft. Often, when leakage occurs,blood fills the aneurysmal sac due to gaps forming between the graft andthe inner wall of the vessel. When vascular grafts fail due to leakage,the patient's condition is often compromised. Thus, it would beadvantageous to provide systems and devices which reduce the risk ofleakage. At least some of these objectives will be achieved by theinventions described hereinafter.

BRIEF SUMMARY OF THE INVENTION

The present invention provides apparatuses, systems and methods fortreating a patient by positioning an expandable body having one or moremicrostructures within a body lumen and penetrating the lumen wall withthe microstructures. The microstructures are formed in or attached tothe expandable body in a low profile fashion suitable for atraumaticintroduction to the body lumen with the use of a catheter or othersuitable device. Each microstructure has an end which is attached to theexpandable body and a free end. Once the apparatus is positioned withinthe body lumen in a desired location, the body is expanded and themicrostructures deploy to a position wherein the free ends projectradially outwardly. The free ends of the deployed microstructures thenpenetrate the lumen wall by continued expansion of the body.Additionally, a therapeutic agent may be delivered to the lumen wall bythe microstructures. When the expandable body comprises a stent, themechanism may be left in place, the microstructures providing anchoringand sealing against the lumen wall. When the body comprises a portion ofan instrument, the expandable body may be retracted after delivery ofthe therapeutic agent and removed.

According to a first aspect of the present invention, an apparatus isprovided comprising an expandable body having a proximal end, a distalend, and a longitudinal axis. The apparatus further includes at leastone microstructure having an attached end attached to the body and afree end. The at least one microstructure is moveable from an undeployedposition to a deployed position wherein the free end projects radiallyoutwardly from the longitudinal axis. In the undeployed position, themicrostructures are typically substantially aligned with an outersurface or perimeter of the body. However, it may be appreciated thatthe microstructures may lie beneath the surface, just so as the freeends do not project substantially outward beyond the surface.

Typically, the at least one microstructure has a directional axisbetween the free end and the attached end. The directional axis of eachmicrostructure may extend in any direction. For example, eachmicrostructure may be arranged so that its directional axis extendsalong the longitudinal axis, such as in a parallel manner.Alternatively, each microstructure may be arranged so that itsdirectional axis extends across the longitudinal axis at an angle, suchas in a perpendicular manner. Thus, the microstructures may be deployedto project radially outwardly regardless of their arrangement andorientation of their directional axes. Although the deployedmicrostructures may extend radially any distance from the expandablebody, a distance of between 25 μm and 5000 μm is preferred.

In preferred embodiments, the expandable body comprises a series ofinterconnected solid sections having spaces therebetween, such asresembling a conventional vascular stent. However, in contrast toconventional stents, the at least one microstructure is formed by atleast one of the solid sections. In some embodiments, expansion of thebody creates forces within the body causing mechanical deformation ofthe solid sections. This in turn deploys the microstructures. Since theapparatus relies upon the utilization of such mechanical deformation ofthe body to deploy the microstructures, additional processing beyondconventional laser machining is not necessary to create themicrostructures.

In some embodiments, each microstructure has first and second supportsand a free end, the supports affixed to associated first and secondadjacent portions of the radially expandable body. Expansion of theexpandable body within the patient effects relative movement between theassociated first and second portions of the expandable body, therelative movement deploying the microstructures.

The expandable body can have any shape including a cylindrical shapesimilar to the overall shape of conventional stents. These shapes,particularly cylindrical shapes, have a circumference. Thus, relativemovement of the associated first and second portions of the expandablebody may comprise circumferential movement of the first portion relativeto the second portion. Although the associated first and second portionsmay move circumferentially as the body expands, the portions may or maynot be circumferentially aligned. In some embodiments wherein theassociated first and second portions are in circumferential alignment,the circumferential movement of the first portion relative to the secondportion draws the free end toward the circumferential alignment. In someof these and other embodiments, the circumferential movement pulls theaffixed ends of the first and second supports apart which moves the freeend. When the expandable body includes an interior lumen (such as astent) configured for receiving an expandable member(such as a ballooncatheter) movement of the free end may create friction against theexpandable member as the expandable member expands the expandable body,the friction projecting the free end radially outwardly.

In some preferred embodiments, the first and second supports compriseelongate shafts extending between the free end and the associated firstand second adjacent portions of the radially expandable body. Therelative movement of the associated first and second portions of theexpandable may comprise moving the associated first and second portionsapart so that the supports pull the free end in opposite directionscausing the free end to project radially outwardly. Often the elongateshafts are adjacent to each other and aligned with a circumference ofthe expandable body in the undeployed position. Thus, expansion of thebody maintains the adjacent positioning of the shafts but moves themapart.

In some preferred embodiments, each microstructure further includes athird support affixed to an associated third potion of the radiallyexpandable body, the associated first and third portions being connectedso as to move in unison. Often, the first, second and third supportscomprise elongate shafts attached to the free end and the associatedfirst, second and third adjacent portions of the radially expandablebody, respectively. Typically, the second support is disposedlongitudinally between the first and third supports. Thus, the relativemovement of the associated first and second portions of the expandablebody can move the associated first and second portions apart while theassociated third portion moves in unison with the associated portion sothat the supports pull the free end in opposite directions forming atripod structure which projects the free end radially outwardly.

In other preferred embodiments, the expandable body has an inner ringand an outer ring surrounding a longitudinal axis. The rings form alumen having a cross-sectional diameter. In addition, at least onemicrostructure is included, each microstructure having a first support,a second support and a free end. The first support is affixed to theinner ring and the second support is affixed to the outer ring.Expansion of the expandable body effects relative movement between theinner ring and outer ring which deploy the microstructures.

And, in still other preferred embodiments, the expandable body having aninner lumen and at least one microstructure having an attached end, afree end and a protruding region between the attached end and the freeend. The protruding region may take any form or shape, such as formingan angle between the attached end and the free end. Typically, themicrostructures are deployable by applying force to the protrudingregion from within the inner lumen. Depending on the shape of theprotruding region, such force may be applied in a variety of directionsto achieve deployment of the microstructures.

In a second aspect of the present invention, a material is providedwhich is carried by the at least one microstructure, wherein thematerial is delivered to the patient upon deployment of the apparatus.The material may include drugs, RNA, DNA, genes, genes encoding fornitric oxide synthase or vascular endothelial growth factor, prednisone,low molecular weight heparin or low molecular weight hirudin,Rapamycin/Sirolimus, Paclitaxel, Tacrolimus, Everolimus, Tyrphostin AG1295, CGS-21680 Hydrochloride, AM 80, Estradiol, Anti-sense compounds,E2F Decoys (see Nakamura, T. et al. “Molecular strategy usingcis-element ‘decoy’ of E2F binding site inhibits neointimal formation inporcine balloon-injured coronary artery model”, in Gene Therapy (2002)9, 488-494), incorporated herein by reference for all purposes), othertherapeutic agents to be delivered to the lumen wall for therapeuticpurposes, or any combination of these.

The material may be carried by the at least one microstructure in avariety of ways. For example, the material may be coated on a surface ofthe at least one microstructure or held in a lumen within the at leastone microstructure. When the material comprises DNA, the microstructuresmay be coated with an adhesive material to which DNA adheres, such asgold. The material may also be coated with a hydrogel polymer orbiocompatible material which provides a protective coating to the drugsand/or DNA. Alternatively, the material may be housed in a porouscoating deposited onto and/or etched into the surface of themicrostructures.

As mentioned, the expandable body may comprise an endoluminal stent.Typically, the stent is sized for positioning within a vascular lumen,however it may be appreciated that the stent may be sized forpositioning within a variety of other body lumens. Expansion of the bodymay be achieved by any suitable means, such as by expansion of anexpandable member, such as an inflatable member or balloon, particularlyan angioplasty balloon, within the body or by self-expansion. Typicallythe bodies are comprised of stainless steel, titanium, tantalum,vanadium, cobalt chromium alloys, polymers, or shape-memory alloys, suchas nickel-titanium alloys, which are particularly suitable forself-expansion. The body may be configured to maintain the deployedposition and remain in the lumen, such as to function as a stent, or maybe retracted to the undeployed position for removal.

In a third aspect of the present invention, methods are provided fortreating a patient with the use of an expandable body having a proximalend, a distal end, a longitudinal axis therebetween, and at least onemicrostructure having an end attached to the body and a free end. In oneembodiment, the expandable body is positioned in an undeployed positionwithin a vessel of the patient. The body is then expanded to a deployedposition within the vessel which projects the free end of themicrostructure radially outward from the longitudinal axis andpenetrates a wall of the vessel.

In vascular vessels, the wall of the vessel comprises an intimal layer,a medial layer and an adventitial layer. Expansion of the body may allowpenetration of the free end through at least the intimal layer. Inaddition, expansion the body can penetrate the free end through at leastthe medial layer. As previously mentioned, expanding the body maycomprise inflating an inflatable member within the mechanism so as toincrease its cross-sectional diameter. Alternatively, the body can beself-expanding and expanding the body comprises releasing the body toallow self-expansion.

In some embodiments, the at least one microstructure carries a material,the method of the present invention further comprising delivering thematerial to the patient. When the material is coated on a surface of theat least one microstructure, delivering the material comprisestransferring the material from the surface of the at least onemicrostructure to the penetrated vessel wall. When the material is heldin a lumen within the at least one microstructure, delivering thematerial comprises injecting or somehow allowing the material to enterinto the penetrated vessel wall.

Other objects and advantages of the present invention will becomeapparent from the detailed description to follow, together with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-2 show an ordinary stent before expansion and after deployment,respectively.

FIGS. 3A-3B show plaque build-up inside a coronary artery, and afterconventional balloon angioplasty and stenting, respectively.

FIG. 4 is a perspective view of an embodiment of an apparatus of thepresent invention comprising an expandable body and at least onemicrostructure.

FIGS. 5A-5B provide cross-sectional views of the apparatus of FIG. 4 inthe unexpanded and expanded states, respectively.

FIG. 5C illustrates an embodiment having microstructures extending alongthe length of the body in a substantially uniform pattern.

FIG. 5D illustrates an embodiments having microstructures present nearthe proximal and distal ends.

FIG. 5E illustrates two separate apparatuses partially inserted withinone another or overlapped.

FIGS. 5F-5G illustrate embodiments of apparatus in a curvedconfiguration.

FIGS. 6A-6B, 7A-7B illustrate possible relationships of the directionalaxis of the microstructure to the longitudinal axis of the body.

FIG. 8 illustrates an embodiment of the apparatus wherein themicrostructures are aligned as in FIGS. 6A-6B, and FIG. 8A provides anexploded view of a microstructure of FIG. 8.

FIGS. 9A-9B shows the microstructure of FIG. 8A in an undeployed anddeployed position, respectively.

FIGS. 10A-10C illustrate embodiments of the free ends of themicrostructures of FIG. 8A.

FIGS. 11A-11C illustrate an additional embodiment of themicrostructures.

FIG. 12 illustrates an embodiment of the apparatus wherein themicrostructures are aligned as in FIGS. 7A-7B, and FIG. 12A provides anexploded view of a microstructure of FIG. 12.

FIG. 13A illustrates circumferential movement of associated first andsecond portions when the portions are circumferentially aligned whileFIG. 13B illustrates circunferential movement of the portions when theportions are not circumferentially aligned.

FIG. 14A illustrates a representative portion of the radially expandablebody having a cylindrical shape and FIGS. 14B-14C illustrate themovement of the expandable body, particularly the movement of the freeends of the microstructures as the expandable member radially expandsthe body.

FIGS. 15A-15C illustrate embodiments of the free ends of themicrostructures of FIG. 12A.

FIGS. 15D-15G illustrate embodiments of the apparatus having variousdesigns.

FIG. 15H illustrates the embodiment depicted in FIG. 15G having themicrostructures in a deployed position.

FIG. 15I provides a schematic cross sectional view of FIG. 15H.

FIGS. 16A-16C illustrate an embodiment including inner and outer rings,relative movement between which deploy the microstructures.

FIGS. 17A-17C illustrate an additional embodiment of the presentinvention wherein expansion of the expandable member and deployment ofthe microstructures may be achieved independently.

FIGS. 18-18A illustrate embodiments of the apparatus including internallumens for delivery of therapeutic material.

FIG. 19 illustrates a cross-sectional view of the expandable bodyexpanded inside a blood vessel lumen, and FIG. 19A provides an explodedview of a microstructure penetrating the wall of the vessel lumen.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description illustrates the invention by way ofexample, not by way of limitation of the principles of the invention.Referring to FIG. 4, an embodiment of an apparatus 10 of the presentinvention is illustrated, the apparatus 10 comprises an expandable body12 and at least one microstructure 14. The expandable body 12 has aproximal end 16, a distal end 18, a longitudinal axis 20 therebetween. Across-sectional diameter 24 is also shown. In this embodiment, theexpandable body 12 comprises a cylindrical structure surrounding thelongitudinal axis 20. However, it may be appreciated that the expandablebody 12 can comprise any shaped structure, including oval,hemispherical, ellipsoidal, spherical, square, rectangular, orpolygonal, to name a few, and may be symmetrical or non-symmetrical.Further, the expandable body 12 may be sized and shaped for deliveryfrom a catheter or other suitable device for positioning within a bodylumen. The embodiment of FIG. 4 is suitable for permanent placementwithin the body lumen, such as to resemble a conventional vascularstent. However, it may be appreciated that the expandable body 12 may beformed as a portion of an instrument which is used to treat a body lumenand is then removed. For example, the expandable body 12 may be expandedwithin a body lumen to deploy the microstructures, the wall of the lumenpenetrated by the microstructures and treated by delivery of drugs orother material from the microstructures to the lumen wall, and theexpandable body 12 then retracted and removed.

Together, the microstructures 14 and the expandable body 12 form thecylindrical structure surrounding the longitudinal axis 20. FIG. 4illustrates the apparatus 10 in an unexpanded state wherein themicrostructures 14 are in an undeployed position. Here, themicrostructures 14 are preferably aligned or flush with an outer surface22 of body 12 so that the surface 22 does not include substantialprotrusions. Alternatively, the microstructures 14 may be positionedbelow the surface 22.

FIGS. 5A-5B provide cross-sectional views of the apparatus 10 of FIG. 4in the unexpanded and expanded states, respectively. FIG. 5A shows thewall of the body 12 within which lie microstructures 14, highlighted byshading. Thus, when the expandable body 12 is in the unexpanded state,the microstructures 14 are in an undeployed position which is alignedwith the surface 22. FIG. 5B illustrates the expandable body 12 in anexpanded state wherein the cross-sectional diameter 24 is increased.Here, the microstructures 14 are in a deployed position wherein a freeend 32 of each microstructure 14 projects radially outward from thelongitudinal axis 20 while an attached end 30 remains attached to thebody 12. As will be described later, in some embodiments the mechanicalact of expansion of the body 12 creates forces which deploy themicrostructures 14. It may be appreciated that the deployedmicrostructures 14 may form any angle with the surface 22, including asubstantially 90 degree angle as shown. Further, differentmicrostructures 14 may form different angles, angles may vary randomlyor in a pattern, angles may be selectable particularly based on amountof expansion, and some microstructures may not deploy while othersdeploy.

It may be appreciated that any number of microstructures 14 may bepresent and may be arranged in a variety of patterns along the entirelength of the body 12 or along any subportion. Referring to FIG. 5C, anembodiment is illustrated having microstructures 14 extending along thelength of the body 12 in a substantially uniform pattern. Themicrostructures 14 are illustrated in deployed positions for ease ofidentification and visualization. Alternatively, for example,microstructures 14 may be present along one side of the expandable body12 and not the other. Or, as illustrated in FIG. 5D, microstructures 14may be present near the proximal end 16 and distal end 18 and nottherebetween. Likewise, microstructures 14 may only be present near oneof the ends 16, 18. This may be particularly useful in delivery oftherapeutic agents to the peri-vascular or peri-adventitial areas ofblood vessels where such agents are more mobile and less dependent onmultiple delivery locations. Referring now to FIG. 5E, two separateapparatuses 10 are shown partially inserted within one another oroverlapped. By arranging the microstructures 14 near the ends 16, 18,the overlapping of the expandable bodies 12 does not result inoverlapping of microstructures 14. This ensures that no portion of theapparatus 10 or overlapped apparatuses will contain more than a singlelayer of microstructures 14. However, it may be appreciated that anynumber of apparatuses 10 with any arrangement of microstructures 14 maybe used, particularly if an abundance of microstructures 14 are desiredto be present.

Although the previous embodiments have been illustrated in a straight orlinear configuration, the apparatuses 10 of the present invention may bepositioned in a variety of curved, angled or twisted configurations whenplaced within body lumens. Body lumens, particularly blood lumens or thevasculature, include segments which are non-linear. FIGS. 5F-5Gillustrate embodiments of apparatus 10 in a curved configuration. Whenmicrostructures 14 are present along a midsection of the expandable body12, as shown in FIG. 5F, the curvature of the body 12 directs themicrostructures 14 along inner arc 15 to concentrate in a small areaThis may be desirable for targeting a specific area with therapeuticagents. However, if such concentration is not desired, microstructures14 may alternatively be arranged near the ends 16, 18 so thatmicrostructures 14 along inner arc 15 are not concentrated, as shown inFIG. 5G. It may be appreciated that the microstructures 14 mayalternatively be arranged near end 16 only, near end 18 only or alongany portion of the apparatus 10.

Any spacing between the microstructures 14 may also be used, preferablybetween 5 microns and 10,000 microns. Deployed microstructures haveheights which may vary but are typically sufficient to penetrate thelumen wall to a desired depth. This may require traversal of thethickness of the compressed plaque. Thus, the deployed microstructuresmay have heights which vary from less than 25 μm to over 5000 μM.

As illustrated in FIG. 4, the expandable body 12 may comprise a seriesof interconnected solid sections 36 having spaces 35 therebetween. Inpreferred embodiments, the expandable body 12 comprises an endoluminalstent. Although such stents may be introduced into various body lumens,such as within the lungs, gastrointestinal tract, urethra, or ureter, toname a few, stents are commonly used in the vascular system,particularly the coronary arteries. Conventional vascular stents aretypically formed from wires bent or woven to define a series ofrelatively tightly spaced convolutions or bends or from a solid metalstructure from which portions are removed in a selected pattern. Theexpandable body 12 of the present invention may resemble conventionalstents and may be similarly manufactured, however the particular designof the structure is dependent upon the microstructures and the way thatthey deploy upon expansion of the body 12. Examples of such designs willbe provided in later sections. Thus, special processing is not necessaryfor the fabrication of the devices of the present invention. Forexample, the expandable body 12 can be laser machined from annealed 316Ltubing; electric discharge machining (EDM) or electrochemical etchingcan also be used to fabricate the devices, to name a few.

As mentioned, each microstructure 14 has an attached end 30, attached tothe body 12, and a free end 32, both in the deployed and undeployedpositions. In preferred embodiments, each microstructure has adirectional axis 40, such as shown in FIG. 6A, between the free end 32and the attached end 30. In some embodiments of the apparatus 10, thedirectional axis 40 extends across the longitudinal axis 20 at an anglewhile the microstructure 14 is in the undeployed position. Here, thedirectional axis 40 is shown to form an angle of approximately 90degrees with the longitudinal axis 20. Deployment of the microstructure14 projects the free end 32 radially outwardly from the longitudinalaxis 20, as shown in FIG. 6B, so that the microstructure 14 extendsbeyond the surface 22. Alternatively, in some embodiments, thedirectional axis 40 extends along the longitudinal axis 20 while themicrostructure 14 is in the undeployed position, as illustrated in FIG.7A. In this case, deployment of the microstructure 14 also projects thefree end 32 radially outward from the longitudinal axis 20, as shown inFIG. 7B, so that the microstructure 14 extends beyond the surface 22.

Generally, the expandable body 12 comprises a series of interconnectedsolid sections having spaces therebetween. The solid sections form thestructure of the expandable body 12 and form the microstructures 14. Inmost embodiments, each microstructure has at least a first support and asecond support and a free end, the first and second supports beingaffixed to associate first and second adjacent portions of the radiallyexpandable body. Expansion of the expandable body effects relativemovement between the associated first and second portions of theexpandable body. For example, the relative movement of the associatedfirst and second portions of the expandable body may comprisecircumferential movement of the first portion relative to the secondportion when the expandable body expands radially. Although thisrelative movement may be in any direction, typically the relativemovement comprises moving the associated first and second portionsapart. Often the circumferential movement pulls the affixed ends of thefirst and second supports apart, which in turn moves the free end. Thus,such relative movement deploys the microstructures from an undeployedposition along the expandable body to a deployed position with the freeend projecting radially outwardly from the longitudinal axis. A varietyof embodiments are provided to illustrate these aspects of the presentinvention.

FIG. 8 illustrates an embodiment of the apparatus 10 wherein themicrostructures 14 are oriented as in FIGS. 6A-6B. Thus, although theapparatus 10 is illustrated in a flat plane, it is formed cylindricallyaround longitudinal axis 20 in this embodiment. As shown, the body 12comprises a series of interconnected solid sections 36 having spaces 35therebetween. A portion of the apparatus 10 including a microstructure14 is illustrated in exploded view in FIG. 8A. Here, a first support 37a, a second support 37 b and a third support 37 c are shown, eachcomprising elongate shafts, wherein the second support 37 b is disposedlongitudinally between the first support 37 aand third support 37 c. Thefirst, second, and third supports 37 a, 37 b, 37 c are attached to thefree end 32 and to first, second and third adjacent portions 38 a, 38 b,38 c, respectively, of the expandable body, as shown. FIG. 9A shows themicrostructure 14 of FIG. 8A wherein the supports 37 a, 37 b, 37 c areadjacent to each other and aligned with a circumference 39 of theexpandable body 12 in the undeployed position. Here, the body 12 is inthe unexpanded state, wherein the cross-sectional diameter has a radiusR₁. FIG. 9B shows the body 12 is in the expanded state, wherein thecross-sectional diameter has a larger radius R₂. Such expansion drawsthe first and second associated portions 38 a, 38 b, apart while theassociated third portion 38 c moves in unison with the associated firstportion 38 a. Thus, the supports 38 a, 38 b, 38 c pull the free end inopposite directions forming a tripod structure which causes the free endto project radially outwardly, as shown.

The free ends 32 of the microstructures 14 depicted in FIG. 8 and FIG.8A are each shown to have a flat-edged shape. However, the free ends 32may have any desired shape. For example, FIGS. 10A-10C illustrateadditional embodiments of microstructures 14 having different shapedfree ends 32. In each of these embodiments, the free ends 32 have apointed shape. When the apparatus 10 is positioned in a body lumen, suchas a blood vessel, the pointed shapes of the free ends 32 may assist inpenetration of the lumen wall. The shape, size and tapering of eachpoint may possibly guide the free end 32 to a certain penetration depth,such as to a specified tissue layer. In FIG. 10A, the free end 32 has asingle point 33 and in FIG. 10B the free end 32 has multiple points 135.In FIG. 10C, the free end 32 has an arrow-shaped point 137. Thearrow-shaped point 137 includes a pointed tip 27 and at least oneundercut 29 to reduce the ability of the free end 32 from withdrawingfrom a lumen wall once penetrated. This may be useful when themicrostructures are used for anchoring. It may be appreciated thatmicrostructures 14 throughout the apparatus 10 may all have the samefree end 32 shape or the shapes may vary randomly or systematically.

FIG. 11A also illustrates an embodiment of the apparatus 10 wherein themicrostructures 14 are oriented as in FIGS. 6A-6B. FIG. 11A provides aportion of the apparatus 10 including the microstructure 14 in explodedview. In this embodiment, the microstructure 14 has first and secondsupports 37 a, 37 b and a free end 32, the supports 37 a, 37 b affixedto associate first and second adjacent portions 38 a, 38 b of theradially expandable body 12. FIG. 11B shows the microstructure 14 ofFIG. 11A wherein the supports 37 a, 37 b are adjacent to each other andaligned with a circumference 39 of the expandable body 12 in theundeployed position. Here, the body 12 is in the unexpanded state,wherein the cross-sectional diameter has a radius R₁. The first andsecond supports 37 a, 37 b comprise elongate shafts extending betweenthe free end 32 and the associated first and second adjacent portions 38a, 38 b of the radially expandable body 12. FIG. 11C shows the body 12is in the expanded state, wherein the cross-sectional diameter has alarger radius R₂. As shown, relative movement of the associated firstand second portions 38 a, 38 bof the expandable body moves theassociated first and second portions 38 a, 38 b apart so that thesupports 37 a, 37 b pull the free end in opposite directions causing thefree end 32 to project radially outwardly.

It may be appreciated that although the free end 32 is illustrated tohave a pointed shape, the free ends 32 may have any desired shape,including the shapes illustrated in FIGS. 10A-10C. And, it may also beappreciated that microstructures 14 throughout the apparatus 10 may allhave the same free end 32 shape or the shapes may vary randomly orsystematically.

FIG. 12 illustrates an embodiment of the apparatus 10 wherein themicrostructures 14 are oriented as in FIGS. 7A-7B. Thus, although theapparatus 10 is illustrated in a flat plane, it is formed cylindricallyaround longitudinal axis 20 in this embodiment. As shown, the expandablebody 12 comprises a series of interconnected solid sections 36 havingspaces 35 therebetween. A portion of the body 12 including amicrostructure 14 is illustrated in exploded view in FIG. 12A. Eachmicrostructure has a first support 37 a, a second support 37 b and afree end 32. The supports 37 a, 37 b are affixed to associate first andsecond adjacent portions 38 a, 38 b of the radially expandable body.

Referring to FIG. 13A, the associated first and second portions 38 a, 38b may be in circumferential alignment, as illustrated by dashed line 41.It may be appreciated that dashed line 41 wraps around to form acircular shape when following the circumference of a cylindrical body,however the dashed line 41 is illustrated as a straight line forclarity. When the expandable body expands radially, the relativemovement of the associated first and second portions 38 a, 38 bmaycomprise circumferential movement of the first portion 38 a relative tothe second portion 38 b, as indicated by arrows 42. When the associatedfirst and second portions 38 a, 38 b may be in circumferentialalignment, as shown, the circumferential movement of the first portion38 a relative to the second portion 38 b draws the free end 32 towardthe circumferential alignment or line 41, as indicated by arrow 44.

Referring to FIG. 13B, the associated first and second portions 38 a, 38b may be in noncircumferential alignment, as illustrated by dashed line46 which forms an angle with line 41 representing circumferentialalignment. Thus, when the expandable body expands radially, the relativemovement of the associated first and second portions 38 a, 38 bmay stillcomprise circumferential movement of the first portion 38 a relative tothe second portion 38 b, as indicated by arrows 42. And, thecircumferential movement of the first portion 38 a relative to thesecond portion 38 b pulls the affixed ends of the first and secondsupports 37 a, 37 b apart which moves the free end 32. However, in thissituation, the free end is no longer drawn toward the circumferentialalignment, rather the free end is drawn toward line 46 as indicated byarrow 48.

FIG. 14A illustrates a representative portion of the radially expandablebody 12 having a cylindrical shape, the remainder of the bodyillustrated by dashed body 12′. In this embodiment the radiallyexpandable body 12 further comprises an interior lumen 52 along thelongitudinal axis 20. The interior lumen 52 may be configured forreceiving an expandable member 54 which expands the expandable body 12,as illustrated. In this case, the expandable member 54 is typicallymounted on a catheter 56. FIGS. 14B-14C illustrate the movement of theexpandable body, particularly the movement of the free ends 32 of themicrostructures 14 as the expandable member 54 radially expands the body12. FIG. 14B is a side view of a portion of the expandable body 12,including a microstructure 14, mounted on expandable member 54.Expansion of the expandable member 54 effects relative movement betweenthe associated first and second portions 38 a, 38 b, in this case suchexpansion effects circumferential movement. Circumferential movement isindicated by arrow 42. It may be appreciated that the associated firstportion 38 a is not shown in FIG. 14B since FIG. 14B is a side view andportion 38 a would be located symmetrically on the backside of theexpandable member 54. The circumferential movement pulls the affixedends of the first and second supports 37 a, 37 b apart which moves thefree end 32, indicated by arrow 48. As shown in FIG. 14C, such movementof the free end 32 projects the free end 32 radially outwardly, asindicated by arrow 60. Such projection may be due to torsionaldeformation of the first and second supports 37 a, 37 b, caused by theincreased separation between the associated first and second portions 38a, 38 b resulting from expansion of the expandable body 12. Suchprojection may also be due to friction created between the free end 32and the expandable member 54 as the expandable member 54 expands theexpandable body 12. Alternatively, such projection may be due to otherfactors, such as the direction of movement of the supports 37 a, 37 b,the shape of the supports 37 a, 37 b, or a combination of factors.

It may be appreciated that the expandable body 12 of FIGS. 14A-14C mayalternatively be expanded by means other than expansion by an expandablemember 54. For example, the expandable body 12 may be self-expanding, aspreviously mentioned. In this situation, the expandable body 12 ispre-formed so that deployment of the body 12 allows the body 12 toself-expand toward a predetermined configuration. Pre-forming may beachieved with the use of an expandable member 54, wherein the body 12 isset while surrounding an expandable member 54 so as to later form thisconfiguration. When the expandable body 12 expands within the body,projection of the microstructures may be due torqueing or movement ofthe supports 37 a, 37 b, for example.

The free ends 32 of the microstructures 14 depicted in FIGS. 12, 12A,13A-13B, 14A-14C are each shown to have a flat-edged shape. However, thefree ends 32 may have any desired shape. For example, FIGS. 15A-15Cillustrate additional embodiments of microstructures 14 having differentshaped free ends 32. In each of these embodiments, the free ends 32 havea pointed shape. When the apparatus 10 is positioned in a body lumen,such as a blood vessel, the pointed shapes of the free ends 32 mayassist in penetration of the lumen wall. The shape, size and tapering ofeach point may possibly guide the free end 32 to a certain penetrationdepth, such as to a specified tissue layer. In FIG. 15A, the free end 32has a single point 33 and in FIG. 15B the free end 32 has multiplepoints 135. In FIG. 15C, the free end 32 has an arrow-shaped point 137.The arrow-shaped point 137 includes a pointed tip 27 and at least oneundercut 29 to reduce the ability of the free end 32 from withdrawingfrom a lumen wall once penetrated. This may be useful when themicrostructures are used for anchoring. It may be appreciated thatmicrostructures 14 throughout the apparatus 10 may all have the samefree end 32 shape or the shapes may vary randomly or systematically.Likewise, the free end 32 may have a flat-shaped inner edge 139, asillustrated in FIG. 15A, to maximize friction against an expandablemember 54 or the free end 32 may have various other shaped inner edges139, as illustrated in FIGS. 15B-15C.

FIGS. 15D-15F illustrate embodiments of the apparatus 10 having variousdesigns. Again, although the apparatus 10 is illustrated in a flatplane, it is formed cylindrically around longitudinal axis 20 in eachembodiment. In FIG. 15D, the microstructures 14 have free ends 32 whichare shaped as a single point 33 and include a flat inner edge 139. Thus,the free ends 32 are similar to the embodiment illustrated in FIG. 15A.FIG. 15E also illustrates an embodiment wherein the microstructures 14have free ends 32 which are shaped as a single point 33 and include aflat inner edge 139. However, in this embodiment, the microstructures 14are positioned more closely together, in a denser pattern. In FIG. 15Fthe microstructures 14 have free ends 32 which are shaped to havemultiple points 135 and to include a flat inner edge 139. In addition,the flat inner edge 139 is part of a flange 43 which is directedopposite of the points 135. The flange 43 provides a wide flat inneredge 139 to maximize friction against an expandable member 54 and anarrow neck region 45 to enhance flexibility and rotation of themultiple points 135 radially outwardly.

FIG. 15G illustrates an embodiment of the expandable body 12 wherein thefree ends 32 of the microstructures 14 have a single point 33 and curvedinner edge 139. And, FIG. 15H illustrates the microstructures of FIG.15G in a deployed position. FIG. 15H provides a view similar to FIG. 14Cwherein circumferential movement pulls the affixed ends of the first andsecond supports 37 a, 37 b apart which moves the free end 32. Suchmovement of the free end 32 projects the free end 32 radially outwardly,as indicated by arrow 60. As mentioned, such projection may be due tofriction created between the free end 32 and the expandable member 54 asthe expandable member 54 expands the expandable body 12.

Alternatively, such projection may be due to other factors, such as thedirection of movement of the supports 37 a, 37 b, the shape of thesupports 37 a, 37 b, or a combination of factors. For example, FIG. 15Iprovides a schematic cross sectional view of FIG. 15H. Prior toexpansion, the free ends 32 and associated first and second portions 38a, 38 b of the expandable member 12 lie substantially equidistant fromthe longitudinal axis 20. Upon expansion of the expandable member 54,the forces are applied to the first support 37 a and second support 37b. Upon further inflation, the first and second supports 37 a, 37 bpresent less resistance to the expandable member 54, and as such theexpandable member 54 expands more in the regions spanned by the firstand second supports 37 a, 37 b than in the regions of the associatedfirst and second portions 38 a, 38 b, as illustrated in FIG. 15I. Thisdeploys the microstructures 14 since there is a contact point betweenthe first and second supports 37 a, 37 b and the expandable member thatserves as a fulcrum about which moment is generated as the expandablemember continues to expand. The resulting moment further projects themicrostructure radially outwardly.

FIGS. 16A-16C illustrate an additional embodiment of the presentinvention. FIG. 16A provides a cross-sectional view of an expandablebody 12, the expandable body 12 having an inner ring 90 and an outerring 92 surrounding the longitudinal axis 20. As shown, the rings 90, 92form an lumen 94 having cross-sectional diameter 24. In addition, atleast one microstructure 14 is included, each microstructure 14 having afirst support 100, a second support 102 and a free end 104. The firstsupport 100 is affixed to the inner ring 90 and the second support 102is affixed to the outer ring 92.

Expansion of the expandable body 12 effects relative movement betweenthe inner ring 90 and outer ring 92, as illustrated in FIG. 16B. Here,diverging lines 90′, 92′ correspond to diverging portions of inner ring90 and outer ring 92, respectively. Since the first support 100 isaffixed to the inner ring 90 and the second support 102 is affixed tothe outer ring 92, the supports 100, 102 are drawn apart as the portionsof the rings 90, 92 diverge. However, the supports 100, 102 arerotateably connected near the free end 104 at a connection point 108.This allows the microstructures to deploy or rotate as shown in FIG.16B.

FIG. 16C illustrates the expandable body 12 of FIG. 16A in an expandedstate wherein the microstructures 14 are deployed. As shown,cross-sectional diameter 12 has increased and the relative movementbetween the inner ring 90 and outer ring 92 has deployed themicrostructures 14 from an undeployed position to a deployed positionwith the free end 104 projecting radially outwardly from thelongitudinal axis 20.

Further, FIGS. 17A-17C illustrate an additional embodiment of thepresent invention. As shown in FIG. 17A, expandable body 12 has aproximal end 16, a distal end 18, a longitudinal axis 20 therebetweenand at least one microstructure 14 having an attached end 30 and a freeend 32 in an undeployed position. In addition, the expandable body 12has an outer surface 110 which in this embodiment is the outer perimeterof the cylindrical expandable body 12. In the undeployed state, theattached end 30 and free end 32 are generally within the outer surface110, either aligned with or below the outer surface 110. This allows theexpandable body 12 to have a low profile in the unexpanded state so thatit may be easily delivered to a body lumen without damage to thedelivery device or lumen wall by protruding free ends 32.

Once positioned within the body lumen in a desired location, themicrostructures 14 may then be deployed. In this embodiment, theexpandable body 12 has an inner lumen 112 and each microstructure 14 hasa protruding region 120 between the attached end 30 and the free end 32.The protruding region 120 may take any form or shape; here theprotruding region 120 forms an angle between the attached end 30 and thefree end 32. Typically, the microstructures 14 are deployable byapplying force to the protruding region 120 from within the inner lumen112. Depending on the shape of the protruding region 120, such force maybe applied in a variety of directions to achieve deployment of themicrostructures 14. For example, as shown in FIG. 17B, themicrostructures 14 maybe deployed by applying force radially outwardlyagainst the protruding region 120 as by expansion of an expandablemember 130 within the inner lumen 112. Here, the expandable member 130is shown mounted on a catheter shaft 134 and inserted through the innerlumen 112. The member 130 is expanded, in this case inflated, and theforce applied to the protruding regions 120 rotates the free ends 32radially outwardly from the longitudinal axis 20. In some embodiments,the attached ends 30 are attached to the expandable body 12 byrotateable joints, however it may be appreciated that the attached ends30 may simply allow rotate of the free ends 32 by bending or mechanicaldeformation near the attached ends 30. Such mechanical deformation maybe particularly suitable for maintaining deployment of themicrostructures.

As shown in FIG. 17C, the expandable member 130 may then be removed anddeployment of the microstructures 14 maintained. Deployment of themicrostructures 14 may be maintained by the apparatus 10 itself, or itmay be maintained by the surrounding lumen wall or plaque through whichthe microstructures may have penetrated. It may be appreciated thatexpansion of the expandable member 130 within the lumen 112 may haveexpanded the expandable body 12, in addition to deploying themicrostructures 14. However, such expansion of the body 12 may beindependent of deployment of the microstructures 14. Thus, theexpandable body 12 be expanded once the microstructures 14 havedeployed, as in FIG. 17C.

As mentioned, penetration of the lumen wall by one or moremicrostructures can be used to anchor the apparatus 10 within the lumenor to deliver drugs, genes or other therapeutic agents or material to orthrough the lumen wall. The material may be coated on a surface of themicrostructures. When the material comprises DNA, each microstructuremay be coated with an adhesive material to which DNA adheres, such asgold. Preferably, when the material comprises DNA, the material is agene encoding for nitric oxide synthase or vascular endothelial growthfactor. Nitric oxide synthase inhibits smooth muscle cells from growingand inhibits platelet and white blood cells adherence to denudedsurfaces following coronary intervention. Vascular endothelial growthfactor stimulates reendothelialization of an injured vessel. To increasethe amount of drugs or genes held by the microstructures, the structuralmaterial could be made porous. A straightforward way of accomplishingthis goal is to anodize the metal forming the apparatus or to coat themetal with a material which is then anodized. Anodization produces ahigh density of small, vertically oriented pores, of which the size andconfiguration can be controlled by varying the anodization current,temperature and solution concentration.

Further, the material may be coated with a biocompatible material whichprovides a protective coating to prevent the drug or gene from beingwashed away, and allows for the release of the drug and/or gene over aperiod of time. Such coatings include biodegradable materials, polymers,hydrogels, and porous ceramics. When the material is a drug which doesnot include DNA, the material is preferably Sirolimus or Paclitaxel.Sirolimus is a macrocyclic lactone with potent immunosuppressiveeffects. Sirolimus binds to an intracellular receptor protein andelevated p27 levels, which leads to the inhibition ofcyclin/cyclin-dependent kinase complexes and, ultimately, inducescell-cycle arrest in the late G1phase. It inhibits the proliferation ofboth rat and human smooth muscle cells in vitro, and reduces intimalthickening in models of vascular injury. Paclitaxel is a taxoid which isused in chemotherapy. Paclitaxel binds to microtubules and inhibitstheir deploymerization into tubulin. This effectively stops the cellsability to breakdown the mitotic spindle during mitosis, preventing celldivision and proliferation. Paclitaxel has also been shown to reduceintimal thickening in models of vascular injury.

Alternatively, as illustrated in FIGS. 18-18A, the material may be heldin one or more internal lumens within the microstructures. FIG. 18illustrates an embodiment of the apparatus 10 similar to the embodimentillustrated in FIG. 12. Here, the free ends 32 are shown to have pointedshapes. Each internal lumen 70 extends through a microstructure 14 toits free end 32. Thus, material within the lumen 70 is expelled from thefree end 32 into the surrounding body lumen or tissue. The material canbe actively pumped by a delivery microsystem or allowed to diffuse outof the lumen 70. Various types of delivery microsystems may be used,including electro-osmotic pumps, shape-memory transducers, expansion ofpolymer gels (such as water-absorbing polyacrylamid gel), osmotic pumps,piezo-electric actuators, electrostatic or electromagnetic pumps, orelectro-dissolution of membranes (Santini, J. et al. “Acontrolled-release microchip”, in Nature, Vol 397, Jan. 28, 1999,incorporated herein by reference for all purposes) to release thematerial followed by diffusion through lumen, to name a few. In theembodiment illustrated in FIG. 18A, the delivery microsystem includes areservoir 72 within the associate first portion 38 aof the expandablebody 12 wherein lumen 70 extends through the first support 37 a from thereservoir 72. The reservoir 72 may simply house the material, or thereservoir 72 may include a therapeutic delivery control device 74. Thisdevice 74 can be designed to release the material at predeterminedintervals. The intervals may be based on pumping timing, controlleddiffusion or triggering by an external signal. The external trigger maybe in the form of a radiofrequency signal, an injectable chemicalsignal, such as an enzyme, or an ultrasonic signal, to name a few.Alternatively or in addition, cells (transplant or xenograft) may beencapsulated in an immuno-isolated device in the reservoir 72. Thiswould allow cellular factories to be implanted that could be fed on theintraluminal side by nutrients, oxygen, etc., in the blood supply. Thus,the reservoir 72 may include a filter which allows contact with theblood supply. Therapeutic material generated by the cells may then bedelivered to the vessel wall, particularly the adventitia Additionally,this system can work in reverse, with the device lumen serving as aconduit for nutrients from the adventitia into the vessel.

As mentioned previously, the present invention may be utilized for anysort of treatment which involves delivery of a therapeutic agent and/oranchoring of a device. The devices could be introduced into various bodylumens, such as the vascular system, lungs, gastro-intestinal tract,urethra or ureter. The function of the microstructures includes but isnot limited to facilitating drug and gene delivery, securing the devicein place and providing a mechanical seal to the lumen wall.

Positioning of the apparatus of the present invention is typicallyperformed via standard catheterization techniques. These methods arewell known to cardiac physicians and are described in detail in manystandard references. Examples of such positioning will be provided inrelation to the vascular system, however, such example is not intendedto limit the scope of the invention. In brief, percutaneous access ofthe femoral or brachial arteries is obtained with standard needles,guide wires, sheaths, and catheters. After engagement of the coronaryarteries with a hollow guiding catheter, a wire is passed across thecoronary stenosis where the apparatus is to be deployed. The apparatusis then passed over this wire, using standard coronary interventionaltechniques, to the site of atherosclerotic coronary plaque where drugand/or gene therapy is to be delivered.

The apparatus is then delivered and expanded to force themicrostructures 14 through the atherosclerotic plaque, so themicrostructure tips reach the vessel wall, as shown in FIGS. 19-19A.FIG. 19 shows a cross-sectional view of the expandable body 12 expandedinside a blood vessel lumen L. Microstructures 14 pierce through thelayer of compressed plaque 3 and into the wall of the lumen L. FIG. 19Aprovides an exploded view of a microstructure 14 penetrating the wall ofthe lumen L. Here, an intimal layer L medial layer M and adventitiallayer A are shown. The microstructure 14 may penetrate any or all of thelayers I, M, A, including penetrating through the wall of the lumen L tothe peri-adventitial space. FIG. 19A illustrates penetration to theadventitial layer A. Penetration allows for more efficient transfer oftherapeutic material into the blood vessel wall, and, when desired, intothe adventitial layer A. When delivering certain therapeutic materials,application from the endovascular space has lead to localization in theintima and inner media. This may be due to physical forces that augmentdrug transport through the arterial wall, for example, in the presenceof convective forces that arise from physiological transmural pressuregradients. However, such delivery may not be sufficient for localizingtherapeutic material in the adventitial layer. Perivascular release hasled to the highest concentrations within the adventitial layer [Creel,C. et al. “Arterial Paclitaxel Distribution and Deposition” inCirculation Research, 2000;86:879-884]. Thus, in some cases it may bedesired to penetrate the microstructures through to the peri-adventitialspace. The therapeutic material which coats or is held within themicrostructures then enters the lumen wall or is depositedperi-vascularly where it performs its desired biological function. Ifthe apparatus is intended to function in a stent-like manner, theapparatus is then left behind in its expanded state. Alternatively, ifthe apparatus is simply intended for delivery of an agent, the apparatusmay be retracted and removed.

Although the invention has been described in detail in the foregoingembodiments for the purpose of illustration, it is to be understood thatsuch detail is solely for that purpose and that variations can be madetherein by those skilled in the art without departing from the spiritand scope of the invention except as it may be described by thefollowing claims.

1. An apparatus for treating a patient comprising: an expandable bodyhaving a proximal end, a distal end, a longitudinal axis therebetween,and at least one microstructure having an attached end attached to thebody and a free end in an undeployed position along the expandable body,expansion of the body creating forces which deploy the at least onemicrostructure from the undeployed position to a deployed positionwherein the free end projects radially outwardly from the expandablebody.
 2. An apparatus as in claim 1, wherein the at least onemicrostructure has a directional axis between the free end and theattached end, and wherein the directional axis extends along thelongitudinal axis while the at least one microstructure is in theundeployed position.
 3. An apparatus as in claim 1, wherein the at leastone microstructure has a directional axis between the free end and theattached end, and wherein the directional axis extends across thelongitudinal axis while the at least one microstructure is in theundeployed position.
 4. An apparatus as in claim 1, wherein the free endhas a pointed shape.
 5. An apparatus as in claim 4, wherein the pointedshape includes a single point, a multiple point, an arrow shaped pointincluding a pointed tip and at least one undercut, or a combination ofthese.
 6. An apparatus as in claim 1, wherein the free end has aflat-edged shape.
 7. An apparatus as in claim 1, further comprising amaterial carried by the at least one microstructure, wherein thematerial is delivered to the patient by the at least one microstructure.8. An apparatus as in claim 7, wherein the material comprises at least agene, at least a drug or a combination of these.
 9. An apparatus as inclaim 7, wherein the material is coated on a surface of the at least onemicrostructure.
 10. An apparatus as in claim 7, wherein the material isheld in a lumen within the at least one microstructure.
 11. An apparatusas in claim 1, wherein the expandable body comprises an endoluminalstent.
 12. An apparatus as in claim 11, wherein the stent is sized forpositioning within a vascular lumen.
 13. An apparatus as in claim 11,wherein the stent is configured to maintain the deployed position andremain in the lumen.
 14. An apparatus as in claim I, wherein theexpandable body is retractable to the undeployed position.
 15. Anapparatus as in claim 1, wherein the expandable body is comprised ofshape-memory alloy, stainless steel, titanium, tantalum, vanadium,cobalt chromium alloy, polymer, or a combination of these.
 16. Anapparatus for treating a patient comprising: a radially expandable bodyhaving a proximal end, a distal end, a longitudinal axis therebetween,and a plurality of microstructures, each microstructure having first andsecond supports and a free end, the supports affixed to associate firstand second adjacent portions of the radially expandable body, expansionof the expandable body within the patient effecting relative movementbetween the associated first and second portions of the expandable body,the relative movement deploying the microstructures from an undeployedposition along the expandable body to a deployed position with the freeend projecting radially outwardly from the expandable body.
 17. Anapparatus as in claim 16, wherein the at least one microstructure has adirectional axis between the free end and the associate first and secondadjacent portions, and wherein the directional axis extends along thelongitudinal axis while the at least one microstructure is in theundeployed position.
 18. An apparatus as in claim 16, wherein the atleast one microstructure has a directional axis between the free end andthe associate first and second adjacent portions, and wherein thedirectional axis extends across the longitudinal axis while the at leastone microstructure is in the undeployed position.
 19. An apparatus as inclaim 16, wherein the microstructures extend radially a distance ofbetween 25 μm and 5000 μm from the radially expandable body.
 20. Anapparatus as in claim 16, wherein the free end has a pointed shape. 21.An apparatus as in claim 20, wherein the pointed shape includes a singlepoint, a multiple point, an arrow shaped point including a pointed tipand at least one undercut, or a combination of these.
 22. An apparatusas in claim 16, wherein the relative movement of the associated firstand second portions of the expandable body comprises circumferentialmovement of the first portion relative to the second portion when theexpandable body expands radially.
 23. An apparatus as in claim 22,wherein the associated first and second portions are in circumferentialalignment and the circumferential movement of the first portion relativeto the second portion draws the free end toward the circumferentialalignment.
 24. An apparatus as in claim 22, wherein the circumferentialmovement pulls the affixed ends of the first and second supports apartwhich moves the free end.
 25. An apparatus as in claim 24, the radiallyexpandable body further comprising an interior lumen along thelongitudinal axis configured for receiving an expandable member whichexpands the expandable body, wherein the movement of the free endcreates friction against the expandable member as the expandable memberexpands the expandable body, the friction projecting the free endradially outwardly.
 26. An apparatus as in claim 24, the radiallyexpandable body further comprising an interior lumen along thelongitudinal axis configured for receiving an expandable member whichexpands the expandable body, wherein expansion of the expandable body bythe expandable member pulls the affixed ends of the first and secondsupports apart which torsionally deforms the first and second supportsprojecting the free end radially outwardly.
 27. An apparatus as in claim24, wherein the radially expandable body is self-expanding composed andthe self-expansion of the expandable body pulls the affixed ends of thefirst and second supports apart which torsionally deforms the first andsecond supports projecting the free end radially outwardly.
 28. Anapparatus as in claim 16, wherein the first and second supports compriseelongate shafts extending between the free end and the associated firstand second adjacent portions of the radially expandable body.
 29. Anapparatus as in claim 28, wherein the relative movement of theassociated first and second portions of the expandable body comprisesmoving the associated first and second portions apart so that thesupports pull the free end in opposite directions causing the free endto project radially outwardly.
 30. An apparatus as in claim 28, whereinthe elongate shafts are adjacent to each other and aligned with acircumference of the expandable body in the undeployed position.
 31. Anapparatus as in claim 16, wherein each microstructure further comprisesa third support affixed to an associated third portion of the radiallyexpandable body, the associated first and third portions being connectedso as to move in unison.
 32. An apparatus as in claim 31, wherein thefirst, second and third supports comprise elongate shafts attached tothe free end and to the associated first, second and third adjacentportions of the radially expandable body, respectively, and wherein thesecond support is disposed longitudinally between the first and thirdsupports.
 33. An apparatus as in claim 32, wherein the relative movementof the associated first and second portions of the expandable bodycomprises moving the associated first and second portions apart whilethe associated third portion moves in unison with the associated firstportion, so that the supports pull the free end in opposite directionsforming a tripod structure which projects the free end radiallyoutwardly.
 34. An apparatus as in claim 1, wherein the at least onemicrostructure comprises a plurality of microstructures disposed nearthe proximal end and/or the distal end and not therebetween.
 35. Anapparatus as in claim 1, wherein the at least one microstructurecomprises a plurality of microstructures disposed between the proximaland distal ends and not substantially near the ends.
 36. A system fortreating a patient comprising: an expandable body having a proximal end,a distal end, and at least one deployable microstructure, whereinexpansion of the body deploys the at least one microstructure to projectradially outward from the expandable body; and a material carried by theat least one microstructure, wherein the material is delivered to thepatient by the at least one microstructure.
 37. A system as in claim 36,wherein the material is coated on a surface of the at least onemicrostructure.
 38. An apparatus as in claim 36, wherein the at leastone microstructure includes a lumen and the material is held in thelumen.
 39. An apparatus as in claim 38, wherein the expandable bodyfurther includes a delivery microsystem and the material is delivered tothe lumen from the delivery microsystem.
 40. An apparatus as in claim39, wherein the delivery microsystem includes a therapeutic deliverycontrol device which delivers the material to the lumen at predeterminedintervals.
 41. An apparatus as in claim 40, wherein delivery istriggered by an external signal in the form of a radiofrequency signal,an injectable chemical signal, an ultrasonic signal or a combination ofthese.
 42. A system as in claim 36, wherein the material comprises atleast a gene, at least a drug or a combination of these.
 43. A system asin claim 42, wherein the material comprises a gene encoding for nitricoxide synthase or vascular endothelial growth factor.
 44. A system as inclaim 42, wherein the material comprises prednisone, low molecularweight heparin, low molecular weight hirudin, Rapamycin/Sirolimus,Paclitaxel, Tacrolimus, Everolimus, Tyrphostin AG 1295, CGS-21680Hydrochloride, AM 80, Estradiol, Anti-sense compounds, E2F Decoys, or acombination of these.
 45. A system as in claim 42, wherein the materialcomprises DNA and an adhesive material to which DNA adheres.
 46. Asystem as in claim 42, wherein the material comprises a biocompatiblematerial which provides a protective coating to the drugs and/or genes.47. A method of treating a patient comprising the steps of: providing anexpandable body having a proximal end, a distal end, a longitudinal axistherebetween and at least one microstructure having an end attached tothe body and a free end; positioning the expandable body within a vesselof the patient, wherein the at least one microstructure is in anundeployed position; and expanding the body within the vessel so thatforces are created which deploy the at least one microstructure, thefree ends of the deployed microstructures projecting radially outwardfrom the expandable body.
 48. A method as in claim 47, furthercomprising expanding the body so that the deployed at least onemicrostructure penetrates the vessel wall.
 49. A method as in claim 48,wherein the body comprises a stent and penetration of the vessel wallanchors the stent within the vessel.
 50. A method as in claim 48,wherein the wall of the vessel comprises an intimal layer, a mediallayer and an adventitial layer, and wherein expanding the bodypenetrates the free end through at least the intimal layer.
 51. A methodas in claim 50, wherein expanding the body penetrates the free endthrough at least the medial layer.
 52. A method as in claim 47, whereinexpanding the body comprises inflating a inflatable member within thebody so as to increase its cross-sectional diameter.
 53. A method as inclaim 47, wherein the body is self-expanding and expanding the bodycomprises releasing the body to allow self-expansion.
 54. A method as inclaim 47, wherein the at least one microstructure carries a material andfurther comprising delivering the material to the patient.
 55. A methodas in claim 54, further comprising expanding the body so that thedeployed at least one microstructure penetrates the vessel wall, whereinthe material is coated on a surface of the at least one microstructureand delivering the material comprises transferring the material from thesurface of the at least one microstructure to the penetrated vesselwall.
 56. A method as in claim 54, further comprising expanding the bodyso that the deployed at least one microstructure penetrates the vesselwall, wherein the material is held in a lumen within the at least onemicrostructure, and delivering the material comprises injecting thematerial into the penetrated vessel wall.
 57. A method as in claim 54,wherein the material comprises at least a gene, at least a drug or acombination of these.
 58. A method for treating a patient comprising thesteps of: providing an expandable body having a proximal end, a distalend, and at least one deployable microstructure carrying a material;positioning the expandable body in an undeployed position within avessel of the patient; expanding the body to a deployed position withinthe vessel, wherein expansion of the structure deploys the at least onemicrostructure to project radially outward from the expandable body;penetrating a wall of the vessel with the at least one microstructure;and delivering the material from the at least one microstructure to thewall of the vessel.
 59. A method as in claim 58, wherein the material iscoated on a surface of the at least one microstructure and deliveringthe material comprises transferring the material from the surface of theat least one microstructure to the penetrated vessel wall.
 60. A methodas in claim 58, wherein the material is held in a lumen within the atleast one microstructure, and delivering the material comprisesinjecting the material into the penetrated vessel wall.
 61. A method asin claim 58, wherein the material comprises at least a gene, at least adrug or a combination of these.
 62. A method as in claim 58, whereinexpanding the body comprises inflating a inflatable member within thebody so as to increase its cross-sectional diameter.
 63. A method as inclaim 58, wherein structure is self-expanding and expanding thestructure comprises releasing the structure to allow self-expansion. 64.An apparatus for treating a patient comprising: an expandable bodyhaving an inner ring and an outer ring surrounding a longitudinal axis;and at least one microstructure, each microstructure having first andsecond supports and a free end, the first support affixed to the innerring and a second support affixed to the outer ring, expansion of theexpandable body within the patient effecting relative movement betweenthe inner ring and the outer ring, the relative movement deploying theat least one microstructure from an undeployed position to a deployedposition with the free end projecting radially outwardly from theexpandable body.
 65. An apparatus as in claim 64, wherein the first andsecond supports are rotateably connected near the free end.
 66. Anapparatus as in claim 64, wherein the microstructures extend radially adistance between 25 μm and 5000 μm from the radially expandable body.67. An apparatus as in claim 64, wherein the free end has a pointedshape.
 68. An apparatus as in claim 67, wherein the pointed shapeincludes a single point, a multiple point, an arrow shaped pointincluding a pointed tip and at least one undercut, or a combination ofthese.
 69. An apparatus as in claim 64, further comprising a materialcarried by the at least one microstructure, wherein the material isdelivered to the patient by the at least one microstructure.
 70. Anapparatus as in claim 69, wherein the material comprises at least agene, at least a drug or a combination of these.
 71. An apparatus fortreating a patient comprising: an expandable body having a proximal end,a distal end, a longitudinal axis therebetween, and at least onemicrostructure having an attached end attached to the body and a freeend in an undeployed position, the at least one microstructuredeployable by rotation of the free end radially outwardly from theexpandable body.
 72. An apparatus as in claim 71, wherein the expandablebody has an outer surface and wherein the attached and free ends arealigned with the outer surface in the undeployed position.
 73. Anapparatus as in claim 71, wherein the expandable body has an inner lumenand the at least one microstructure has a protruding region between theattached end and the free end which protrudes into the inner lumen, theat least one microstructure deployable by applying a force to theprotruding region from within the inner lumen.
 74. An apparatus as inclaim 73, wherein the at least one microstructure is deployable byapplying force radially outwardly against the protruding region.
 75. Anapparatus as in claim 74, wherein the at least one microstructure isdeployable by applying force radially outwardly against the protrudingregion by expansion of an expandable member within the inner lumen. 76.An apparatus as in claim 73, wherein the protruding region forms anangle between the attached end and the free end.
 77. An apparatus as inclaim 71, wherein the attached end is attached to the body by arotateable joint.
 78. An apparatus as in claim 71, further comprising amaterial carried by the at least one microstructure, wherein thematerial is delivered to the patient by the at least one microstructure.79. A method of treating a patient comprising the steps of: providing anexpandable body having a proximal end, a distal end, a longitudinal axistherebetween, an inner lumen and at least one microstructure having anend attached to the body, a free end and a protruding regiontherebetween which protrudes into the inner lumen; positioning theexpandable body within a vessel of the patient, wherein the at least onemicrostructure is in the undeployed position; and applying a forceagainst the protruding region from within the inner lumen which deploysthe at least one microstructure to a deployed position wherein the freeends of the deployed microstructures project radially outwardly from thelongitudinal axis.
 80. A method as in claim 79, wherein applying a forceagainst the protruding region comprises expanding an expandable memberagainst the protruding region.
 81. A method as in claim 80, wherein theexpandable member comprises an inflatable member.
 82. A method as inclaim 79, wherein applying a force against the protruding region rotatesthe free end around the attached end.
 83. A method as in claim 79,further comprising expanding the body so that the deployed at least onemicrostructure penetrates the vessel wall.
 84. A method as in claim 83,wherein expanding the body comprises inflating an inflatable memberwithin the body so as to increase its cross-sectional diameter.
 85. Amethod as in claim 79, wherein the at least one microstructure carries amaterial and further comprising delivering the material to the patient.86. A method as in claim 85, wherein the material comprises at least agene, at least a drug or a combination of these.